Ultrasound has been widely used in medical applications for both diagnostic and therapeutic purposes. Diagnostic imaging is probably the most common application of ultrasound in medicine. The exposure intensity levels for diagnostic ultrasound are below 0.5 W/cm2. At the other end of the spectrum, high intensity focused ultrasound (>1000 W/cm2) is used to destroy tissue to treat cancers and other abnormalities such as arrhythmias in the heart. Ultrasound intensities in the mid-range (e.g., 0.5-3 W/cm2) are used for other therapeutic applications such as in physical therapy or to enhance drug delivery.
A first report on the use of ultrasound to enhance drug delivery used ultrasound to drive hydrocortisone ointment into inflamed tissues for treating poly arthritis. The ultrasound-assisted delivery of drug molecules across the percutaneous barrier to a target area is called ‘phonophoresis’. This technique has been used for several drugs. In addition, ultrasound has also been shown to enhance the effects of several therapeutic drug classes, including chemotherapeutic, thrombolytic, and gene-based drugs. Ultrasound enhances drug delivery through thermal mechanisms as well as non-thermal mechanisms such as cavitation, radiation pressure, and acoustic microstreaming. In some cases, these mechanisms act at the tissue level and in some cases at the cellular level. Transient permeabilization of the cell membrane, which may occur during cavitation, leads to uptake of molecules into the cell. This phenomenon, called ‘sonoporation’, has been confirmed by many studies, also for gene transfer. Sonoporation is often conducted with the help of microbubbles, which are originally developed as contrast agents for diagnostic ultrasound imaging. Local delivery of drugs is important for localized treatment of anomalies such as tumors without harming the surrounding healthy tissue. What is needed is a device and method to improve the efficiency of the local treatment and to monitor localized drug delivery of the treatment spot.